Very significantly lower concentrations of diazepam at 15 minutes and 1 hour after 10 mg intravenous diazepam injection were found in chronic alcoholic patients in comparison to healthy controls. Compared to 13 healthy controls a more rapid elimination of diazepam from the plasma of 14 chronic alcoholic patients during their alcohol-free period was observed. The alcoholics had a smaller concentration of the diazepam main metabolite, N-demethyldiazepam, and at 3 hours this difference was significant. The concentrations of free plasma oxazepam as a metabolite of diazepam, were not observed after a single dose of diazepam either in the alcoholics or in volunteers. A more rapid elimination of diazepam after 5 mg/kg intraperitoneally in the plasma of rats pretreated with ethyl alcohol (15 % in drinking water for 3 weeks) was found than in the control rats. Pretreatment of rats with ethyl alcohol increased significantly the concentration of the hydroxylated metabolite, free oxazepam, in the plasma, but not of the demethylated metabolite, N-demethyldiazepam.
Diazepam (tensopam@) 10 mg was given orally t o 12 chronic alcoholic patients, at the beginning of the alcohol-free period and to 14 controls. Diazepam in the plasma was determined gaschromatographically with a B3Ni-EC detector. During the absorption phase the plasma levels of diazepam were reduced to 44 % at 2 hours (P < 0.01) and 32 % at 3.5 hours (P < 0.001) in alcoholic patients compared with respective values of normal subjects. The reduced values, found in the alcoholic patients, may be due to disturbances in the gastro-intestinal absorption of diazepam, or to processes involving the portal vein or liver. Some alcoholic patients received a simultaneous treatment with neuroleptic or hypnotic drugs.
Young ovariectomized female albino rats were treated with gonadal hormones (oestrogen, androgen and progesterone) for half a year, during which time they also received a diet with a high Ca/P-ratio and sugar. The effect of this treatment on the body weight and the weight, length, and Ca-, P-, and N-content of the femurs was investigated.
The weight of the femurs given in percentage of the mean initial body weight was significantly lowest in the oestrogen group and highest in the androgen group. The significantly lowest Ca content was observed in the androgen group and also in the progesterone group. In the oestrogen group the value was no higher than that in the control series. The phosphorus content of the femurs was higher for the animals which had undergone hormonal treatment than for the control animals. The N-content in the androgen and progesterone groups, but not in the oestrogen group, was significantly lower as compared with the controls.
It seems likely that a diet with a high Ca/P-ratio, which contains more carbohydrates than an ordinary diet, would not be unfavourable for the calcification of developing bone with regard to the Ca-, P- and N-contents of the bone. Of the gonadal hormones androgen particularly, and to some extent progesterone seem to have a reducing effect on the Ca- and N-contents of the bone under these conditions.
In the 7 psychiatric patients 10 mg diazepam administered intravenously, during continuous therapy, caused a significantly lower increase of diazepam concentrations in the plasma (at 15 min. P < 0.01; 1 hour P < 0.001; 3 and 6 hours P < 0.05; 24 hours P < 0.001) than in 13 healthy volunteers as an indicator of the increased elimination rate of diazepam. As a sign of the increased formation of the main metabolite, the increase in the concentration of N‐demethyldiazepam was significantly higher in the psychiatric patients on continuous diazepam therapy (at 15 min. P < 0.05; 1 hour P < 0.01) than in healthy volunteers. The intravenous injection of 10 mg diazepam caused in 7 psychiatric patients on continuous diazepam therapy a significantly lower mean increase of diazepam concentrations in the plasma (at 15 min., 1 hour, 3 and 6 hours P < 0.01; 24 hours P < 0.001) than in 12 psychiatric patients treated without diazepam and significantly higher increase in the concentrations of N‐demethyldiazepam (at 1 hour P < 0.05). No measurable amounts of free oxazepam was found in the plasma.
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